Bridging Study to Eliminate Presence of MRD for Acute Leukemia Before HCT

NCT ID: NCT02349178

Last Updated: 2020-03-09

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-12-08
• Study Completion Date: 2017-03-16

Brief Summary

This is a Phase 2 study designed for the purpose of estimating various parameters surrounding the efficacy of Clofarabine, Cyclophosphamide and Etoposide in eliminating minimal residual disease (MRD) in acute leukemia patients otherwise in remission and without causing significant delay of HCT due to treatment related toxicity.

A single course of "bridge" chemotherapy is given prior to the transplant procedure as an approach to improved disease-free survival in a patient group who historically has had inferior outcomes.

Detailed Description

Study entry is open to patients regardless of gender or ethnic background.

The intent of this study design is for all patients to receive and complete one course of therapy. Patients who exhibit signs of disease progression or experience an unacceptable toxicity will be discontinued from treatment.

There will be no dose delays or dose reductions of study drugs for hematologic toxicity during Consolidation "Bridging" therapy (Day 1 through Day 30); however, prolonged hematopoietic recovery or bone marrow aplasia during the first 42 days may meet a study stopping rule.

Conditions

Leukemia, Acute Lymphoblastic; Acute Myeloid Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Bridging Arm

Days 1-5 Receive 20 mg/m2 IV Clofarabine (CLOLAR) over 2 hours followed by 100 mg/m2 IV Etoposide (VP-16, Etopophos) over 2 hours followed by 300 mg/m2 IV Cyclophosphamide (Cytoxan, CTX) as a 30-60 minute infusion

Group Type: EXPERIMENTAL

Clofarabine

Intervention Type: DRUG

Days 1-5 receive Clofarabine 20 mg/m2 IV over 2 hours

Cyclophosphamide

Intervention Type: DRUG

Days 1-5 receive Cyclophosphamide 300 mg/m2 IV as a 30-60 minute infusion

Etoposide

Intervention Type: DRUG

Days 1-5 receive Etoposide 100 mg/m2 IV over 2 hours

Interventions

Clofarabine

Days 1-5 receive Clofarabine 20 mg/m2 IV over 2 hours

Intervention Type: DRUG

Cyclophosphamide

Days 1-5 receive Cyclophosphamide 300 mg/m2 IV as a 30-60 minute infusion

Intervention Type: DRUG

Etoposide

Days 1-5 receive Etoposide 100 mg/m2 IV over 2 hours

Intervention Type: DRUG

Other Intervention Names

CLOLAR; Cytoxan, CTX; VP-16, Etopophos

Eligibility Criteria

Inclusion Criteria

• Diagnosis of acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) with < 5% blasts in the bone marrow (M1) by morphology and that meets one of the following criteria:

Flow cytometric evidence of MRD (≥ 0.01% leukemic blasts for ALL or ≥ 0.5% leukemic blasts for AML detected in the bone marrow) OR Molecular/cytogenetic evidence of disease (FISH or PCR methodology) performed within 7 days And with the intent of going on to an allogeneic hematopoietic cell transplantation (HCT) independent of this study

• Patients must have an available donor and have intention of proceeding directly to ALL-HCT after completion of 1 cycle of Bridging therapy.
• Age 0 to 39 years
• Karnofsky Performance Status ≥ 50% for patients 16 years and older and Lansky Play Score ≥ 50 for patients under 16 years of age (see Appendix 2)
• Patients must have a life expectancy ≥ 8 weeks as determined by the enrolling investigator
• Have acceptable organ function as defined within 7 days of study registration

Renal: creatinine clearance ≥ 60 mL/min/1.73 m2 or serum creatinine based on age/gender as follows:

Hepatic: ALT < 5 x upper limit of normal (ULN) and total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age Cardiac: left ventricular ejection fraction ≥ 40% by ECHO/MUGA

• Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study. At least 7 days must have elapsed from prior chemotherapy.
• Hematopoietic Growth Factors: At least 7 days since the completion of therapy with a growth factor and at least 14 days since pegfilgrastim (Neulasta®) administration.
• Sexually active females of child bearing potential must agree to use adequate contraception (diaphragm, birth control pills, injections, intrauterine device [IUD], surgical sterilization, subcutaneous implants, or abstinence, etc.) for the duration of treatment and for 2 months after the last dose of chemotherapy. Sexually active men must agree to use barrier contraceptive for the duration of treatment and for 2 months after the last dose of chemotherapy.
• Voluntary written consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.

Exclusion Criteria

• Acute Promyelocytic Leukemia (APL)
• Active extramedullary disease (CNS ≥ CNS2 and/or testicular leukemia) or presence of chloromatous disease
• Receiving concomitant chemotherapy, radiation therapy; immunotherapy or other anti-cancer therapy other than is specified in the protocol
• Systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment)
• Pregnant or lactating. The agents used in this study are known to be teratogenic to a fetus and there is no information on the excretion of agents into breast milk. All females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy.
• Known allergy to any of the agents or their ingredients used in this study
• Participating in a concomitant Phase 1 or 2 study

• Maximum Eligible Age: 39 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

American Family Children's Hospital

OTHER

Sponsor Role: collaborator

Nationwide Children's Hospital

OTHER

Sponsor Role: collaborator

Medical College of Wisconsin

OTHER

Sponsor Role: lead

Responsible Party

Michael Burke

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Michael J Burke, MD

Role: PRINCIPAL_INVESTIGATOR

Medical College of Wisconsin

Locations

Nationwide Children's Hospital

Columbus, Ohio, United States

American Family Children's Hospital

Madison, Wisconsin, United States

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, United States

Froedtert Memorial Lutheran Hospital

Milwaukee, Wisconsin, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

Bridging

Identifier Type: -

Identifier Source: org_study_id